Since its establishment in 1994, and again since its first competitive renewal in 1999, the Harvard Skin Disease Research Center (HSDRC) has continued to succeed in achieving its primary goals; 1) to identify and recruit outstanding scientists from the general biomedical community who work in areas relevant to pathophysiology of the skin and skin disease, and 2) to build skin disease research into a strong interdisciplinary presence within the Harvard biomedical community. A secondary goal has been to "leverage" the HSDRC designation of the new Brigham and Women's Hospital Dermatology Department into the establishment of new resources and strong programs spanning basic research to clinical dermatology, to the ultimate benefit of patients with skin diseases. Specific accomplishments since 1998 include 1) An increase in the research base to include 98 individuals from nine Harvard-affiliated institutions, 2) a 23-fold return on investment of Pilot and Feasibility Funding, 3) more than 150 manuscripts published in peer reviewed journals as a result of HSDRC funding, 4) three international conferences sponsored wholly or in part by the HSDRC, 5) the funding of a five year, $15M Specialized Program of Research Excellence (SPORE) grant based at Brigham and Women's Hospital, 6) the granting of full "Program" Status to the Cutaneous Oncology and Melanoma Program (COMP) of the Dana Farber Harvard Comprehensive Cancer Center, 7) the establishment of the Department of Dermatology at Brigham and Women's Hospital (formerly a Division of the Department of Medicine), 8) recruitment of several new research and clinical faculty, 9) movement of Brigham Dermatology Associates to larger, newly renovated dedicated space, 10) the assignment of an additional 6,000 net assignable square feet (NASF) to the Dermatology Department/HSDRC, 11) an active enrichment program, and 12) ongoing commitment from BWH and Medical School leadership to sustain and support the HSDRC. We propose the modification and continuation of four productive Core facilities: the Transgenic Models Core, the Cell Culture Core, the Leukocyte Migration Core, and the Confocal Fluorescence Imaging Core. An ancillary core, based on siRNA Technology, will be funded by Departmental reserves. In addition, new and innovative Pilot and Feasibility Projects are proposed. With the present proposal, the HSDRC is poised to continue to fulfill its important mission on behalf of patients with skin disease.